Financial Data and Key Metrics Changes - The company has identified a new development candidate for its parathyroid hormone receptor program, moving forward after unexpected findings with a previous compound [3][5] - The new compound, SEP-479, shows significantly improved pharmaceutical properties compared to the discontinued SEP-786, with a lower effective dose in preclinical models [9][10] Business Line Data and Key Metrics Changes - The parathyroid hormone receptor program has transitioned to SEP-479, which has demonstrated the ability to normalize serum calcium levels in preclinical models [9][10] - The MRGPRX2 program has initiated a phase one trial with a randomized, placebo-controlled design, focusing on skin-based indications [14][15] Market Data and Key Metrics Changes - The company has formed a collaboration with Novo Nordisk, which includes a $195 million upfront payment and covers all R&D costs going forward, allowing the company to expand its programs without increasing its burn rate [46][47] Company Strategy and Development Direction - The company is focused on GPCR drug discovery, utilizing its Native Complex Platform to optimize compounds quickly and effectively [2][4] - The strategic partnership with Novo Nordisk aims to leverage their expertise in the metabolic space while pursuing multiple programs in parallel [46][47] - The company is exploring additional opportunities in areas such as osteoporosis, neurology, cardiovascular diseases, and respiratory diseases [50][51] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the connection between preclinical data and eventual patient data for PTH peptides, indicating a strong potential for the new compound [21][22] - The company aims to gather safety and pharmacokinetic data in phase one trials to inform future patient dosing strategies [23][24] Other Important Information - The company has completed additional studies on SEP-786 to understand its effects better, particularly regarding bilirubin metabolism [7][8] - The company is optimistic about the potential for once-daily dosing with SEP-479, which could significantly improve patient compliance [31][32] Q&A Session Summary Question: When did the company start to see issues with bilirubin in the SINOS study for SEP-786? - The company observed bilirubin issues within a couple of days in the SINOS study, similar to findings in patients [18] Question: What is the development plan for SEP-479? - The company plans to conduct a phase one study with hopes of seeing safety and pharmacokinetic properties that will inform patient dosing [20][22] Question: How does SEP-479 differ from SEP-786? - SEP-479 is a completely different structural series with no observed functional differences in assays, but it is expected to have a lower risk of off-target effects [29][30] Question: What is the expected timeline for the phase one trial? - The company anticipates starting the phase one trial in the first half of next year, with more precise timing to be communicated later [34] Question: What is the opportunity within mast cell diseases for the MRGPRX2 program? - The company sees potential in various mast cell-driven diseases, including chronic spontaneous urticaria and atopic dermatitis, and plans to pursue multiple lead indications [35][40]

Core Insights - Septerna, Inc. is advancing its next-generation oral small molecule PTH1R agonist program for hypoparathyroidism, with plans to select a development candidate in Q3 2025 and initiate a Phase 1 clinical trial in H1 2026 [2][3] - The company is also initiating a Phase 1 clinical trial for SEP-631, an oral small molecule for mast cell diseases, in Q3 2025 [7] - Septerna's cash position is strong, with $379.2 million in cash and equivalents as of June 30, 2025, and an expected cash runway extending into 2029 following a $195 million upfront payment from Novo Nordisk [12][15] PTH1R Agonist Program - The PTH1R agonist program aims to provide full-day calcium control for patients with hypoparathyroidism, with a development candidate selection expected in Q3 2025 [3] - A Phase 1 clinical trial is planned to commence in the first half of 2026 after successful preclinical development [3] SEP-631 MRGPRX2 NAM Program - SEP-631 is a selective oral small molecule MRGPRX2 negative allosteric modulator for mast cell diseases, with a Phase 1 trial to assess safety and tolerability in healthy volunteers starting in Q3 2025 [7] Collaboration with Novo Nordisk - A global collaboration and license agreement with Novo Nordisk became effective on July 1, 2025, focusing on the discovery and development of oral small molecule therapies for obesity, type 2 diabetes, and other cardiometabolic diseases [7] - Septerna received a $195 million upfront payment as part of this collaboration [7] Business Highlights - The company continues to progress its TSHR NAM program, moving multiple lead compounds closer to development candidate selection for treating Graves' disease and thyroid eye disease [7] - Septerna's discovery-stage programs are advancing across various therapeutic areas utilizing its Native Complex Platform™ [7] Financial Results - For Q2 2025, Septerna reported R&D expenses of $22.2 million, up from $15.0 million in Q2 2024, and G&A expenses of $6.9 million, compared to $3.4 million in the same period [12] - The net loss for Q2 2025 was $24.8 million, compared to a net loss of $16.4 million in Q2 2024 [12][14]